FULL PAPER: Caligiuri et al. (2009). Handwriting for Monitoring Schizophrenia drugs

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Handwriting Movement Analyses for Monitoring Drug-Induced Motor Side Effects in Schizophrenia Patients Treated with Risperidone
Michael P. Caligiuri, Ph.D.,1 Hans-Leo Teulings, Ph.D.,2 Charles E. Dean, M.D.,3 Alexander B. Niculescu, III, M.D., Ph.D.,4 and James Lohr, M.D.1

1University of California, San Diego, CA
2NeuroScript LLC, Tempe AZ
3Minneapolis VA, Minneapolis MN
4 Indiana University School of Medicine and Indianapolis VA Medical Center, IN
Address Editorial Correspondence to: Michael P. Caligiuri, Ph.D., University of California, Department of Psychiatry (0603), 9500 Gilman Drive, La Jolla, CA 92093, Email: mcaligiuri@ucsd.edu
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Abstract. Epidemiologic studies indicate that nearly 60% of schizophrenia (SZ) patients treated with conventional antipsychotic drugs develop extrapyramidal side effects (EPS) such as parkinsonism and tardive dyskinesia. Although the prevalence of EPS has decreased due to the newer antipsychotics, EPS continue to limit the effectiveness of these medicines. Ongoing monitoring of EPS is likely to improve treatment outcome or compliance and reduce the frequency of re-hospitalization. A quantitative analysis of handwriting kinematics was used to evaluate effects of antipsychotic medication type and dose in schizophrenia patients. Twenty-seven schizophrenia patients treated with risperidone, six schizophrenia patients who received no antipsychotic medication and 46 healthy comparison participants were enrolled. Participants performed a 20-minute handwriting task consisting of loops of various sizes and a sentence. Data were captured and analyzed using MovAlyzeR software. Results indicated that risperidone-treated participants exhibited significantly more dysfluent handwriting movements than either healthy or untreated SZ participants. Risperidone-treated participants exhibited lower movement velocities during production of simple loops compared to unmedicated patients. Handwriting dysfluency during sentence writing increased with dose. A 3-factor model consisting of kinematic variables derived from sentence writing accounted for 83% (r = .91) of the variability in medication dose. In contrast, we found no association between observer-based EPS severity ratings and medication dose. These findings support the importance of handwriting-based measures to monitor EPS in medicated schizophrenia patients.

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Psychiatry Res. 2010 May 15;177(1-2):77-83. Epub 2010 Apr 9.
Handwriting movement kinematics for quantifying extrapyramidal side effects in patients treated with atypical antipsychotics.
Caligiuri MP, Teulings HL, Dean CE, Niculescu AB 3rd, Lohr JB.
Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. mcaligiuri@ucsd.edu

Abstract
Ongoing monitoring of neuroleptic-induced extrapyramidal side effects (EPS) is important to maximize treatment outcome, improve medication adherence and reduce re-hospitalization. Traditional approaches for assessing EPS such as Parkinsonism, tardive akathisia, or dyskinesia rely upon clinical ratings. However, these observer-based EPS severity ratings can be unreliable and are subject to examiner bias. In contrast, quantitative instrumental methods are less subject to bias. Most instrumental methods have only limited clinical utility because of their complexity and costs. This paper describes an easy-to-use instrumental approach based on handwriting movements for quantifying EPS. Here, we present findings from psychiatric patients treated with atypical (second generation) antipsychotics. The handwriting task consisted of a sentence written several times within a 2 cm vertical boundary at a comfortable speed using an inkless pen and digitizing tablet. Kinematic variables including movement duration, peak vertical velocity and the number of acceleration peaks, and average normalized jerk (a measure of smoothness) for each up or down stroke and their submovements were analyzed. Results from 59 psychosis patients and 46 healthy comparison subjects revealed significant slowing and dysfluency in patients compared to controls. We observed differences across medications and daily dose. These findings support the ecological validity of handwriting movement analysis as an objective behavioral biomarker for quantifying the effects of antipsychotic medication and dose on the motor system.